Association of hemoglobin, albumin, lymphocyte, and platelet score with risk of cerebrovascular, cardiovascular, and all-cause mortality in the general population: results from the NHANES 1999-2018.

Background and aims: Cardiovascular and cerebrovascular disease (CCDs) contribute to leading causes of morbidity and mortality in the United States of America (USA). Hemoglobin, albumin, lymphocyte, and platelet (HALP) score, a simple and convenient indicator, could reflect the combination of inflammation and nutritional status. This study was undertaken to evaluate the associations between HALP score and risk of cardiovascular, cerebrovascular, and all-cause mortality in the general population from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Methods: We identified 21,578 participants during the 1999-2018 cycles of the NHANES in this research. HALP score was calculated as hemoglobin (g/L) × albumin (g/L) × lymphocytes (/L)/platelets (/L). Outcomes were cerebrovascular, cardiovascular, and all-cause mortality determined by the NHANES-linked National Death Index record and followed until 31 December 2019. Survey-weighted Cox regression, restricted cubic spline analysis, and subgroup analysis were applied to investigate relationships between HALP score and risk of mortality. Results: This cohort study comprised 49.2% male and 50.8% female, of which the median age was 47 years old. In multivariate survey-weighted Cox regression adjusting for all confounders, compared with participants with low HALP scores, participants with highest HALP score had a lower risk of all-cause mortality (adjusted HR:0.80, 95% CI: 0.73, 0.89, P < 0.0001) and cardiovascular mortality (adjusted HR:0.61, 95% CI: 0.50, 0.75, P < 0.0001), and mediate HALP score had the lowest risk of all-cause mortality (adjusted HR:0.68, 95% CI: 0.62, 0.75, P < 0.0001) and cardiovascular mortality (adjusted HR:0.60, 95% CI: 0.48, 0.75, P < 0.0001). Restricted cubic spline analysis showed a non-linear relationship between HALP score and cardiovascular and all-cause mortality (all P values <0.001). Conclusion: HALP score was independently associated with risk of cardiovascular and all-cause mortality, but not cerebrovascular mortality.

The Association Between Admission Anemia and Poststroke Depression.

ABSTRACT: Poststroke depression (PSD) is the most frequent and important neuropsychiatric problem afflicting these patients. Anemia is common in many of these individuals presenting with acute stroke. This study determined whether there is a relationship between anemia on hospital admission and PSD. Two hundred eighty-four acute stroke patients were included in the study. Among them, there were 88 PSD patients, whereas another 196 were non-PSD patients. Clinical depression symptoms were diagnosed according to DSM-4 (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria and a HAMD-17 (the 17-item Hamilton Depression Scale) score ≥8 at 1 month after stroke. In the PSD patients, 27.3% of them presented with anemia, whereas only 12.8% of the non-PSD patients had this condition. There was a negative correlation between hemoglobin level and HAMD-17 score in all patients. A binary logistic regression analysis revealed that anemia was independently associated with PSD after adjustment for sex, National Institutes of Health Stroke Scale scores, mRS (modified Rankin Scale) scores, BI (Barthel Index) scores, RBC (red blood cell), and hematocrit. In conclusion, anemia at admission is associated with PSD seen in these patients 1 month later. Therefore, anemia is a possible predictor of PSD.

Reduced thiamine is a predictor for cognitive impairment of cerebral infarction.

OBJECTIVE: Reduced thiamine (vitamin B1 ) had been reported to be associated with cognitive impairment caused by Alzheimer disease. Our study is to explore the association between thiamine and cognitive impairment after acute ischemic stroke. MATERIALS AND METHODS: One hundred and eighty two patients with acute cerebral infarction were recruited within the first 24 hr after admission. Thiamine and other vitamin Bs of peripheral blood samples were measured. Patients were divided into with poststroke cognitive impairment (PSCI) and non-PSCI according to the score of MMSE and the degree of education. RESULTS: Reduced thiamine (<1.0 ng/ml) was independently associated with PSCI (OR: 2.033, 95% CI: 1.017-4.067, p = .045) after adjusting for potential confounding factors. Advanced age, lower education, diabetes mellitus, left hemisphere infarction, and higher National Institute of Health Stroke Scale (NIHSS) were also independent risk factors for PSCI. CONCLUSIONS: Reduced thiamine is one of the predictors for early cognitive impairment in patients with acute cerebral infarction.

The association between interleukin-8 levels and the development of withdrawal symptoms during methamphetamine abstinence.

OBJECTIVE: Withdrawal symptoms are common during methamphetamine (METH) abstinence. This study aimed to explore the association between serum interleukins and withdrawal symptoms during METH abstinence. METHODS: This study recruited 120 METH users, and 94 of them completed the 2-week follow-up. Serum interleukin-1ß, 6,8,10 were tested at admission. Withdrawal symptoms were assessed by the Methamphetamine Withdrawal Questionnaire (MAWQ). RESULTS: Serum IL-8 levels were positively correlated with MAWQ scores at the 2-week endpoint (r = .257, p = .013). The variation of the MAWQ scores during the 2-week follow-up was negatively correlated with serum IL-8 levels at admission (r = -.249, p = .026). Serum IL-8 levels remained associated with the severity of METH withdrawal symptoms (ß = .363, p = .023), after adjusting for potential confounders. LIMITATIONS: This study did not include normal controls. Most patients were male and cigarette smokers. Patients were only followed up for 2 weeks, and their toxicology data were not collected. Interleukins were only measured at admission, and were tested in serum, not in the cerebrospinal fluid. CONCLUSIONS: Our study demonstrated that higher serum IL-8 levels may predict more severe withdrawal symptoms at 2 weeks after METH abstinence.

Post-Stroke Depression and Estimated Glomerular Filtration Rate: A Prospective Stroke Cohort.

PURPOSE: Post-stroke depression (PSD) is a frequent comorbidity in patients presenting with acute ischemic stroke. Impaired kidney function has been associated with depression in non-stroke subjects. We would like to evaluate whether the estimated glomerular filtration rate (eGFR) on admission is associated with the development of PSD. PATIENTS AND METHODS: Total of 268 patients with acute ischemic stroke were recruited and completed 1-month follow-up visit. eGFR was calculated from the serum creatinine value, race, age, and sex by using the chronic kidney disease epidemiology collaboration equation (CKD-EPI creatinine equation). The 17-item Hamilton Depression Scale was used to evaluate depression symptoms. Patients with a depression score of ≥7 were evaluated using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition, for diagnosing post-stroke depression at 1 month. Meanwhile, 114 normal control subjects were also recruited. RESULTS: Ninety-three (34.7%) patients were diagnosed as having PSD at 1 month. There was a significant intergroup difference in eGFR levels within 24 hrs after admission (F=13.608, p<0.001). The levels of eGFR within 24 hrs after admission were significantly lower in both non-PSD patients and PSD patients than in normal controls. In logistic regression, the level of eGFR (<82mL/min/1.73m2) was independently associated with increased risk of PSD even after adjusting for confounders (OR=2.328, 95% CI:1.092-4.965, p=0.029). CONCLUSION: Reduced eGFR was found to be correlated with the development of PSD and it suggests the need for greater attentions and potential interventions for depression in patients with stroke and with reduced eGFR.

High levels of plasma fibrinogen are related to post-stroke cognitive impairment.

INTRODUCTION: Studies have shown that high levels of the fibrinogen (FIB) are related to cognitive deficits. However, the relationship between fibrinogen and cognitive deficit after stroke remains unclear. Therefore, we explored the relationship between plasma fibrinogen and post-stroke cognitive impairment (PSCI). METHODS: This study is carried out in the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. A total of 210 patients with acute ischemic stroke were enrolled in this study. Ultimately, 134 patients completed 3-month follow-up. Blood samples were collected at hospital admission. Cognitive function was evaluated 3 months after stroke. All patients underwent the Mini-Mental State Examination (MMSE) after 3 months. RESULTS: Higher levels of fibrinogen were observed in patients with post-stroke cognitive impairment compared with the non-PSCI group (p < .001). Additionally, elevated plasma fibrinogen levels were independently associated with PSCI (odds ratio [OR] = 2.000, 95% CI 1.062-3.770 p = .032). The plasma fibrinogen levels were negatively correlated with the 3-month MMSE scores (r = -.171, p = .048). In a multivariate linear regression, FIB was negatively associated with the 3-month MMSE scores after adjustment for the other variables (ß = -0.782, p = .035). CONCLUSION: High levels of plasma fibrinogen were associated with the presence and severity of PSCI.

Genome-wide screening identifies oncofetal lncRNA Ptn-dt promoting the proliferation of hepatocellular carcinoma cells by regulating the Ptn receptor.

Oncofetal genes are genes that express abundantly in both fetal and tumor tissues yet downregulated or undetected in adult tissues, and can be used as tumor markers for cancer diagnosis and treatment. Meanwhile, long noncoding RNAs (lncRNAs) are known to play crucial roles in the pathogenesis of hepatocellular carcinoma (HCC), including tumor growth, proliferation, metastasis, invasion, and recurrence. We performed a genome-wide screening using microarrays to detect the lncRNA expression profiles in fetal livers, adult livers, and liver cancer tissues from mice to identify oncofetal lncRNAs in HCC. From the microarray data analysis, we identified lncRNA Ptn-dt as a possible oncofetal gene. Both in vitro and in vivo experiments results confirmed that overexpression of Ptn-dt significantly promoted the proliferation of mouse HCC cells. RNA pulldown assay showed that Ptn-dt could interact with the HuR protein. Interestingly, miR-96 binds with HuR to maintain its stability as well. Overexpression of lncRNA Ptn-dt led to the downregulation of miR-96, which might be due to the interaction between Ptn-dt and HuR. Meanwhile, previous studies have reported that Ptn can promote tumor growth and vascular abnormalization via anaplastic lymphoma kinase (Alk) signaling. In our study, we found that overexpression of Ptn-dt could promote the expression of Alk through repressing miR-96 via interacting with HuR, thus enhancing the biologic function of Ptn. In summary, a new oncofetal lncRNA Ptn-dt is identified, and it can promote the proliferation of HCC cells by regulating the HuR/miR-96/Alk pathway and Ptn-Alk axis.

Low levels of serum magnesium are associated with poststroke cognitive impairment in ischemic stroke patients.

PURPOSE: Population-based studies have revealed a high prevalence of cognitive impairment after stroke. We aimed to determine the impact of serum magnesium (Mg2+) levels on the occurrence of poststroke cognitive impairment (PSCI). PATIENTS AND METHODS: Acute ischemic stroke patients (n = 327) were enrolled in our study and serum Mg2+ levels were assessed on admission. The cognitive performance of each patient was evaluated using the Mini-Mental State Examination (MMSE) at a 1-month follow-up visit. RESULTS: One hundred five (32.1%) patients were diagnosed with PSCI at 1-month poststroke. The serum Mg2+ levels in both the PSCI group and the non-PSCI group were significantly lower than those in normal control group (P<0.001). In addition, the PSCI group had lower levels of serum Mg2+ compared to the non-PSCI group (P=0.003). In the binary logistic regression analysis, a serum Mg2+ level of ≤0.82 mmol/L was significantly associated with an increased risk of developing PSCI by the 1-month follow-up (OR 2.236, 95% CI 1.232-4.058, P=0.008), as was age (OR 1.043, 95% CI 1.014-1.073, P=0.003). CONCLUSION: Our results demonstrate the existence of a significant association between low levels of serum Mg2+ and the occurrence of PSCI 1-month poststroke, and these results suggest that low levels of serum Mg2+ on admission may serve as a risk factor for developing PSCI by 1-month poststroke.

Low Tri-iodothyronine Syndrome Is Associated With Cognitive Impairment in Patients With Acute Ischemic Stroke: A Prospective Cohort Study.

OBJECTIVE: Low tri-iodothyronine (T3) syndrome is a predictor of poor prognosis in patients with stroke. Poststroke cognitive impairment (PSCI) is a common and important complication after stroke. The association between low T3 syndrome and PSCI is unclear. We aimed to explore the potential relationship between low T3 syndrome and PSCI in the acute phase of ischemic stroke at a 1-month follow-up visit. METHODS: In total, 314 ischemic stroke patients were consecutively enrolled in the study and followed up at 1 month. Thyroid hormones were measured within 24 hours after admission. Cognitive function was evaluated by the Mini-Mental State Exam (MMSE) 1 month after acute ischemic stroke. Cognitive impairment was defined as an MMSE score of less than 27. Cognitive impairment severity was categorized as severe, mild, or none (MMSE score <23, 23-26, or ≥27, respectively). RESULTS: According to the MMSE score, 182 participants (58.0%) had cognitive impairment 1 month after stroke. Patients with low T3 syndrome were more prone to have cognitive impairment than patients with normal levels of T3 (p < 0.001). After adjusting for potential confounders in our logistic model, low T3 syndrome was independently associated with PSCI (odds ratio 4.319, 95% confidence interval 1.553-12.013, p = 0.005). CONCLUSION: Low T3 syndrome in the acute phase of ischemic stroke was associated with a higher prevalence of 1-month PSCI, independently of established risk factors.

Transcriptome sequencing of a chimaera reveals coordinated expression of anthocyanin biosynthetic genes mediating yellow formation in herbaceous peony (Paeonia lactiflora Pall.).

BACKGROUND: Herbaceous peony (Paeonia lactiflora Pall.) is a traditional flower in China and a wedding attractive flower in worldwide. In its flower colour, yellow is the rarest which is ten times the price of the other colours. However, the breeding of new yellow P. lactiflora varieties using genetic engineering is severely limited due to the little-known biochemical and molecular mechanisms underlying its characteristic formation. RESULTS: In this study, two cDNA libraries generated from P. lactiflora chimaera with red outer-petal and yellow inner-petal were sequenced using an Illumina HiSeq™ 2000 platform. 66,179,398 and 65,481,444 total raw reads from red outer-petal and yellow inner-petal cDNA libraries were generated, which were assembled into 61,431 and 70,359 Unigenes with an average length of 628 and 617 nt, respectively. Moreover, 61,408 non-redundant All-unigenes were obtained, with 37,511 All-unigenes (61.08%) annotated in public databases. In addition, 6,345 All-unigenes were differentially expressed between the red outer-petal and yellow inner-petal, with 3,899 up-regulated and 2,446 down-regulated All-unigenes, and the flavonoid metabolic pathway related to colour development was identified using the Kyoto encyclopedia of genes and genomes database (KEGG). Subsequently, the expression patterns of 10 candidate differentially expressed genes (DEGs) involved in the flavonoid metabolic pathway were examined, and flavonoids were qualitatively and quantitatively analysed. Numerous anthoxanthins (flavone and flavonol) and a few anthocyanins were detected in the yellow inner-petal, which were all lower than those in the red outer-petal due to the low expression levels of the phenylalanine ammonialyase gene (PlPAL), flavonol synthase gene (PlFLS), dihydroflavonol 4-reductase gene (PlDFR), anthocyanidin synthase gene (PlANS), anthocyanidin 3-O-glucosyltransferase gene (Pl3GT) and anthocyanidin 5-O-glucosyltransferase gene (Pl5GT). CONCLUSION: Transcriptome sequencing (RNA-Seq) analysis based on the high throughput sequencing technology was an efficient approach to identify critical genes in P. lactiflora and other non-model plants. The flavonoid metabolic pathway and glucide metabolic pathway were identified as relatived yellow formation in P. lactiflora, PlPAL, PlFLS, PlDFR, PlANS, Pl3GT and Pl5GT were selected as potential candidates involved in flavonoid metabolic pathway, which inducing inhibition of anthocyanin biosynthesis mediated yellow formation in P. lactiflora. This study could lay a theoretical foundation for breeding new yellow P. lactiflora varieties.

Silk porous scaffolds with nanofibrous microstructures and tunable properties.

Scaffold biomaterials derived from silk fibroin have been widely used in tissue engineering. However, mimicking the nanofibrous structures of the extracellular matrix (ECM) for achieving better biocompatibility remains a challenge. Here, we design a mild self-assembly approach to prepare nanofibrous scaffolds from silk fibroin solution. Silk nanofibers were self-assembled by slowly concentrating process in aqueous solution without any cross-linker or toxic solvent and then were further fabricated into porous scaffolds with pore size of about 200-250µm through lyophilization, mimicking nano and micro structures of ECM. Gradient water/methanol annealing treatments were used to control the secondary structures, mechanical properties, and degradation behaviors of the scaffolds, which would be critical for different tissue regeneration applications. With salt-leached silk scaffold as control, the ECM-mimetic scaffolds with different secondary structures were used to culture the amniotic fluid-derived stem cells in vitro to confirm their biocompatibility. All the ECM-mimetic scaffolds with different secondary structures represented better cell growth and proliferation compared to the salt-leached scaffold, confirming the critical influence of ECM-mimetic structure on biocompatibility. Although further studies such as cell differentiation behaviours are still necessary for clarifying the influence of microstructures and secondary conformational compositions, our study provides promising scaffold candidate that is suitable for different tissue regenerations.

Nanoscale Control of Silks for Nanofibrous Scaffold Formation with Improved Porous Structure.

Silk-based porous scaffolds have been used extensively in tissue engineering because of their excellent biocompatibility, tunable biodegradability and robust mechanical properties. Although many silk-based scaffolds have been prepared through freeze-drying, a challenge remains to effectively control porous structures during this process. In the present study silk fibroin with different nanostructures were self-assembled in aqueous solution by repeated drying-dissolving process and then used to improve porous structure formation in lyophilization process. Viscosity, secondary structures and water interactions were also studied to exclude their influence on the formation and control of porous structures. Following nanofiber formation in aqueous solution, silk scaffolds with improved porous structure were directly formed after lyophilization and then stabilized with water or methanol annealing treatments. Compared to silk scaffolds derived from fresh solution, the nanofibrous scaffolds showed significantly better cell compatibility in vitro. Therefore, this nanoscale control of silk offers feasible way to regulate the matrix features including porous structure and nanostructure, which are important in regulating cell and tissue outcomes in tissue engineering and regeneration, and then achieve silk-based scaffolds with improved properties.